The role of descending noradrenergic systems in regulation of nociception: the effects of intrathecally administered alpha-adrenoceptor antagonists and clonidine.
It has been proposed that descending noradrenergic systems exercise a tonic inhibition of nociception at the spinal level. The recent finding that changes in tail skin temperature (TT) may have a strong effect on the tail-flick latency makes a reevaluation of this hypothesis necessary. The alpha-adrenoceptor agonist clonidine injected intrathecally (i.th.) in a dose of 60 micrograms increased the response temperature in the increasing hot plate test 10 min after injection, and prolonged the tail-flick latency 30-60 min after injection. A considerable part of the change in tail-flick latency was caused by a reduction in TT. The alpha 1-antagonist prazosin (30 and 60 micrograms) tended to increase the response temperature in the increasing hot plate test after 60 min, and to prolong the latency in the tail-flick test. These effects were not statistically significant. Clonidine and prazosin induced sensorimotor impairment and a reduction in body temperature after 30-60 min. The alpha 2-antagonist yohimbine had no effect in the increasing hot plate test, but reduced the tail-flick latency 10 min after drug administration. This reduction could be explained by an increase in TT. The results suggest that the reduced latency in the tail-flick test after i.th. injection of yohimbine is caused by an increase in the tail blood flow, and does not support the hypothesis of a tonic bulbospinal noradrenergic inhibition of nociception. The time course of response latencies suggests that supraspinal mechanisms may be involved in the effects of i.th. clonidine and prazosin in the tail-flick test, while there seems to be a spinally mediated antinociceptive effect of clonidine that can be demonstrated in the increasing hot plate test.
Tjølsen
Arne
A
Department of Physiology, University of Bergen, BergenNorway.
Lund
Anders
A
Hole
Kjell
K
D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D003000:Clonidine / Q000008:administration & dosage / Q000494:pharmacology*; D007278:Injections, Spinal; D008297:Male; D009619:Nociceptors / Q000502:physiology*; D010147:Pain Measurement; D011597:Psychomotor Performance / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011930:Reaction Time / Q000187:drug effects; D013564:Sympathetic Nervous System / Q000502:physiology*
D003000:Clonidine